Modulation of the innate immune response after trauma visualised by a change in functional PMN phenotype
Introduction
The Acute Respiratory Distress Syndrome (ARDS) is a frequent and severe complication after trauma. Although the mortality and morbidity rates of ARDS have decreased over the last decade, the incidence remains high.2, 28 Polymorphonuclear granulocytes (PMNs) play an essential role in the development of ARDS. In experimental animal models of ARDS, high numbers of PMNs are found in the pulmonary interstitium.4, 29 PMN depletion or blocking of PMN extravasation protects animals for the development of ARDS in severe trauma models.6, 10, 18 This prominent role of PMNs is emphasised by the correlation between the extent of ischaemia reperfusion injury and the accumulation of PMNs in the pulmonary interstitium.25, 26
In patients, PMN activation is mostly measured by static phenotype characteristics or reactive oxygen species (ROS) production, however, with contradictory results. We have recently demonstrated that after trauma PMNs in the peripheral circulation have a decreased responsiveness of active FcγRII, an opsonin receptor related to antibody recognition. This represents the altered functionality of these cells. In the same patients the PMNs in the pulmonary interstitium demonstrated an activated phenotype and function.11 We hypothesised that this altered functional PMN phenotype, measured by PMN receptor analysis in whole blood, could be used as a read out of the inflammatory response to injury. In addition, it was investigated whether these putative changes in PMN responsiveness were associated with the development of signs and symptoms of severe systemic inflammation (systemic inflammatory response syndrome [SIRS] and ARDS).
Section snippets
Patients
Patients with a wide range of injury severity were chosen in order to investigate the relationship between trauma severity and PMN receptor expression. Fifty-two trauma patients with an ISS (Injury Severity Score) >3 and admitted to the Department of Traumatology, University Medical Centre Utrecht were included. Exclusion criteria were age <16 or >80 years, death within 6 h after admission and patients with an altered immunological status (e.g. corticosteroid use or chemotherapy). A blood sample
Patient demographics
Fifty-two consecutive trauma patients were included with varying severities of their injuries. Their mean age was 34 years (interquartile range 20–49) and the mean ISS was 10 (interquartile range 9–17). In total, 12 patients needed transfusion (packed red blood cells). However, in our cohort, only 1 patient required >10 packed red blood cells. Five patients suffered from severe head trauma, moreover, all 5 patients suffered from additional thorax injury. Nine patients fulfilled the SIRS
Discussion
We found a decreased responsiveness of active FcγRII towards the bacterial peptide fMLP on the circulating PMN population after trauma. The extent of this reduced responsiveness correlated with the burden of trauma, estimated by injury severity scores and base deficit levels (Table 6). More importantly, the extent of decrease in fMLP-induced active FcγRII on PMNs was related to severity of the clinical expression of the systemic inflammatory response, such as SIRS and ALI/ARDS.
In contrast, no
Acknowledgement
This project was funded by the AO Foundation, grant S-06-14H.
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Cited by (38)
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2022, InjuryPathophysiology in patients with polytrauma
2022, InjuryCitation Excerpt :It was shown that the immune status of the patient can be determined based on the epitopes that are deployed on the membrane of the neutrophils [74]. Moreover, the PMN phenotype appears to be a readout for the innate immune response [75]. The early assessment of the immune status, as demonstrated by neutrophil phenotype predicted outcome.
Polytrauma management - What is new and what is true in 2020 ?
2021, Journal of Clinical Orthopaedics and TraumaCitation Excerpt :In this line, Pillay and co-workers30 have demonstrated that the immune status of the patient can be determined based on the epitopes that are deployed on the membrane of the neutrophils. Moreover, Hietbrink et al.31 demonstrated that the PMN phenotype is a readout for the innate immune response. This has been further substantiated by an international study from both the Netherlands and South Africa,32 where the immune status, as demonstrated by neutrophil phenotype predicted outcome.
Penetrating thorax injury leads to mild systemic activation of neutrophils without inflammatory complications
2014, InjuryCitation Excerpt :The two patients who developed a septic shock had a decreased fMLF induced active FcγRII expression compared with healthy individuals. Previously we have described this refractory phenotype in neutrophils from multi trauma patients.19 In patients who developed systemic inflammatory complications, such as ALI/ARDS, a decreased responsiveness of active FcγRII on neutrophils was found.
The impact of trauma on neutrophil function
2014, InjuryCitation Excerpt :Upon in vitro stimulation with the bacterial tripeptide formyl-methionine–leucine–phenylalanine (fMLP), neutrophils from subjects that have suffered blunt, penetrative or head trauma fail to up-regulate the receptors CD11b and active FcγRII as efficiently as neutrophils from healthy controls [21,27]. In the case of active FcγRII, fMLP-induced expression of this receptor correlated negatively with injury severity score [27] and was significantly lower on the surface of neutrophils isolated from subjects who subsequently developed secondary complications [22,27]. Thus, following trauma it appears that the responsiveness of circulating neutrophils to bacterial stimulation is suppressed.